Exp. Path., Bd. 14, S. 69-75 (1977) Department of Pathology, University Medical School, Debrecen (Head: Prof. Dr. sc. med. P. ENDES)
The effect of unilateral papillectomy on the juxtaglomerular granulated cells By M. SZOKOL, E. BARANYAI1 ), 1. MIK( 2) and Sz. GOMBA With 2 figures (Received February 27, 1977) Key words: papillectomy; juxtaglomerular granulated cells; glomeruli; renin-angiotensin system macula densa; sodium excretion; glomerular perfusion; kidney; macular cells; glomerular filtration rate; juxtaglomerular index; nephron; tubular sodium load; rat Abbreviations: JCG = juxtaglomerular granulated cells JGI = juxtaglomerular index GFR = glomerular filtration rate
Summary The changes of the juxtaglomerular index values in the superficial, deep and whole cortical areas of rat kidneys after unilateral papillectomy were analyzed. On the papillectomized side the JGI values showed an increase in the deep, and a decrease in the superficial cortical zone. The changes proved to be significant during the whole experimental period in the juxtamedullary index and between the 4~14 postoperative days in the superficial index values. The tendency of the changes of JGI in the contralateral kidneys was similar to those of the papillectomized kidneys, but significant differences were registered less constantly. These changes are probably the consequences of haemodynamic factors. Papillectomy is considered an incompetent model for studying the regulatory function of macula densa in the synthesis of renin.
The macula densa plays an important role in the fine regulation of the glomerular perfusion and sodium excretion (THURAU 1965, 1967, GROSS 1965, STElIlEY 1966, VANDER 1967). The macular cells seem to transmit humoral information to the juxtaglomerular granulated cells (JGC) about the sodium content of the distal tubular fluid (REEVES 1965). These modified smooth muscle cells of the arteriolar wall synthetise renin and are indirectly responsible for the production of angiotensin II. Two different theories explain how the GFR and the sodium excretion are regulated by the renin-angiotensin system. According to THURAU'S conception (1965, 1966, 1967) the high tubular sodium content (concentration) induces renin production and secretion. The secreted renin forms angiotensin "in loco", which gives rise to a contraction of the afferent arterioles lowering the GFR and the rate of filtrated sodium. On the contrary, VANDER et al. (1967) regard the low tubular sodium load as a specific stimulatory effect on the synthesis and secretion of renin. The effect of locally produced angiotensin II may be a contraction in the efferent arterioles followed by a rise in the GFR and an increase of the filtrated sodium. 1) Present address: Pediatric Clinic, University Medical School, Debrecen, Hungary. 2) Present address: Department of Experimental Surgery, University Medical School, Debrecen, Hungary.
69
In order to confirm one of these conceptions and to study the interactions between the macula densa and the juxtaglomerular granulated cells, unilateral papillectomy was performed in the right kidney of rats. Breaking the continuity of some nephrons, first of all the juxtamedullary ones by papillectomy, the "feed-back" mechanism between the macula densa and the glomerular hilus are blocked in the same nephrons, too. The purpose of our investigations was to find out changes in the juxtaglomerular index rates (JGI) after the operation. Within certain limits, the JGI properly represents the functional state of these cells (DEVENYI et aI. 1971, HARTROFT and HARTROFT 1963, DAuDA et aI. 1968).
Material and methods Male Wistar rats of our own breeding weighing about 160-180 g were used for the experiment. Papillectomy was carried out on the right kidneys of 15 animals according to the method of KROON et al. (1962). The parenchyma was incised and the capsule sutured of the right kidneys of 5 sham-operated control rats. A standard normal diet and tap water were offered ad lib. Water intake of all rats was registered on the 3rd, 7th, 13th and 162nd postoperative days. Urine samples were collected in special cages for 24 hours at the same time. Urine volume and specific weight were measured. The specific weight was determined by means of a pycnometer comparing the weight of equal volumes of urine and distilled water at 4°C. On the 4th, 8th, 14th and 163rd days after the operation 4-4 papillectomized rats and 1 control were killed in ether anesthesia by bleeding. Kidneys were fixed in 10% neutralized formol. Blocks were cut out omitting the linear scar of the 6peration and its immediate surroundings and were embedded in paraffin. 5 micron thick sections were stained by hemalum-eosin and by the combined trichrome method (ENDES 1969) in order to visualize the JGC. The JGI was estimated after the method of HARTROFT and HARTROFT (1953) modified by ENDES et al. (1969) counting at lease 400 glomeruli in each kidney. The JGI rates of the whole area of the cortex and the inner (juxeamedullary) corticll zone were determined separately. From these data we calculated the JG I values belonging to the outer cortical zone. In order to count the JGI of the juxtamedullary cortical area, the outer cortical zone was shaded by painting the cover glass with Indian ink under microscopic control. The significance of differences between mean values of JG I, water intake, urinary output and specific weight was estimated by STUDENT'S t-test.
Results The effectiveness of the papillectomy was pointed out by the increase in the daily water intake and urinary output during the postoperative period (table 1). The urinary specific weight was diminished to 1036.7 in comparison with the 1042 control value. All these changes proved to be significant and are similar to the data of the literature referring to bilateral papillectomy (KROON et aI. 1962). The values, measured at unilateral papillectomy are somewhat lower than after bilateral operation. The general histological picture of the papillectomized kidneys was similar to that formed by LUCKE et al. (1968) and DAVIES (1968) except that both tubular atrophy and chronic interstitial inflammation was less pronounced (fig. 1, 2). The JGI rates of the superficial, juxtamedullary, and whole cortical areas in both kidneys of the control rats were identical with the data of the literature (ROJO-ORTEGA and GENEST 1970). Table 1. Some physiological parameters of unilaterally papillectomized and sham-operated control rats (mean values ± SEM) Papillectomized rats n = 60 Water intake
(mlf24 hours)
Urinary volume (mlj24 hours) Urinary specific weight (mg/ml)
36.75 ± 1.28*
25.78
± 1.46
± 0.36*
5.64
± 0.53
± 1.83*
1042.05
8.24 1036.7
*) p < 0.001 as compared with controls.
70
Controls
n = 15
± 2.6
Fig. U',Cut surface of the papillectomy covered by cuboidcylindrical epithelium. 14th day after the operation. HE. x 63.
Fig. 2. Well preserved cortical area in the papillectomized kidney. 7th day after the operation. HE x50.
71
-::J ~
Table 2. Juxtaglomerular index values (JGI) of the superficial, deep and whole cortical areas in the papillectomized and untouched kidneys between the 4-163 postoperative days (mean values ± SEM) Days after the unilateral papillectomy 4 8 14 24 163 Controls
JGI . Papillectomized kidneys cortical area deep super~icial
whole
JGI Untouched kidneys cortical area superficial
± 1.96** 10.00 ± 1.88*** 11.24 ± 1.87*** 19.94 ± 5.18 26.00 ± 2.09 27.62 ± 2.2
± 0.84** 19.41 ± 1.8 18.39 ± 1.93 21.78 ± 1.4 24.5 ± 1.63 22.9 ± 1.79
± 3.09* 21.05 ± 2.53 26.2 ± 3.34 15.08 ± 1.95** 21.9 ± 2.93 27.62 ± 2.2
12.45
± 3.9* 33.21 ± 6.12*** 38.94 ± 3.58*** 30.1 ± 4.37** 22.2 ± 3.11* 13.61 ± 2.94 24.31
* p < 0.05 as compared with controls. ** p < 0.01 as compared with controls. *** p < 0.001 as compared with controls.
16.83
15.93
deep
± 4.02 24.98 ± 3.83* 26.84 ± 2.49** 18.88 ± 2.18 23.0 ± 3.12* ·13.61 ± 2.94 15.82
whole
± 1.72* 23.52 ± 3.26 27.66 ± 1.9 17.21 ± 2.22 20.9 ± 2.35 22.9 ± 1.79 15.65
The most prevalent changes were observed in the juxtamedullary cortical area of the papillectomized kidneys. The JGI values of this area proved to be significantly higher during the whole experimental period as compared to the controls. The peak of the elevation was found on the 8th postoperative day. Thereafter the JGI rates decreased gradually till the 163rd day, but did not sink to the control level. In the superficial cortical area of the papillectomized kidneys the JGI values were·found to be below the control rates. The initial decrease was followed by a gradual elevation till the 163rd day. The differences to the controls are significant on the 4th, 8th, and 14th postoperative days. The changes of the JGI rates in the contralateral kidneys were similar to the papillectomized ones, first of all in the juxtamedullary area, where also an elevation could be registered during the whole experimental period, but values proved to be significantly higher than the controls only on the 8th, 14th, and 163rd days. A significant increase was registered in the superficial index rates on the 4th and 24th days. None of the changes were expressed in the JGI of the whole cortical area except the rates on the 4th postoperative day, when they were decreased significantly both in the right and left kidneys. The mean values and standard errors of the JGI belonging to different cortical zones are summarized in table 2.
Discussion There are no data in the literature about the changes of the JGI after papillectomy. TRIBE and HEPTINSTALL (1965) described hyperplasia and hypergranulation of the JG cells after a simple incision of the cortical and medullary zone of the kidney. The alterations were observed in an irregular distribution in the neighbourhood of the scars, therefore JGI values could not be estimated. Hyperplasia of the JG cells was explained with the scarring. In our material fibrosis or scarring did not occur in the sections used for the estimation of the JGI. We made a distinction between the superficial and deep glomeruli, because the interrupted nephrons were probably situated in the deep cortical area. Only the Henle's loops belonging to the deep nephrons reach the tip of the papilla. The loops of superficial nephrons end at the borderline of the outer and inner medulla (MUNKACSI and PALKOVITS 1966). Among the observed changes of the JGI the increase in the juxtamedullary area seems to be the most distinct one, first of all on the papillectomized side, but this tendency is manifested in the contralateral kidney, too. The elevation on the papillectomized side can be explained by VANDER'S theory (1967): Interrupting the deep nephrons the sodium concentration falls to 0 in the tubular lumen at the level of the macula densa. The increase in the granularity of the JG cell - representing most probably an elevated renin production (DAUDA et al. 1968, DEVENYI et al. 1971) - is elicited by the decreased tubular sodium load. But the subsequent results of our experiment put to issue the validity of the above mentioned conclusion: In the contralateral kidney containing intact nephrons, significantly elevated JGI values were also registered in the deep cortical zone. The observed decrease of the JGI in the bilateral superficial cortical areas cannot be explained by primary changes occuring in the tubular sodium load at the macula densa. It is much more probable that the changes of the JGI in both kidneys are produced by haemodynamic alterations. TOBIAN et al. (1959) and ENDES et al. (1964) traced the hypergranularity of the JG cells back to the decreased stretching of the afferent arteriolar wall and inversely, the hypogranulation back to the increased arteriolar stretching in accordance with the assumed baroreceptor function of these cells. The interruption of the efferent arterioles originating from the juxtamedullary glomeruli (arteriolae rectae spuriae) obviously leads to haemodynamic consequences in the deep cortical area. Further reflectoric changes can be assumed in the circulation of the superficial cortical area of the papillectomized kidney and of both cortical areas of the contralateral kidney.
73
According to the microdissection studies of FLAMENBAUM et al. (1974) decreased blood flow to superficial cortex promotes renin release and results in decreased superficial JGA renin content, while increased deeper cortical flow may inhibit renin release resulting in increased deep JGA renin content. If we consider our superficial and deep JGI values, changes of an opposed sign are to be induced in the superficial and deep cortical circulation, i. e. the blood flow of the deeper cortex probably increased. On the other hand it must be taken into consideration that the granularity of the JG cells is influenced by the synthesis, secretion and storage of renin. That means, the synthetic activity is not characterised by the JGI values alone, but together with the renin concentration in the blood serum and in the renal tissue (DEVENYI et al. 1971). The most reliable parameter of renal renin release is the renin concentration in the blood of renal vein, but this value does not reflect separated superficial and deep cortical renin release. Another factor, which might influence the renin production in papillectomized rats is that these animals are polyuric (KROON et al. 1962, MARSCHALL et al. 1963) and probably mildly sodium losing, although we have not found data in the literature about their sodium metabolism. Considering the "baroreceptor" and "macula densa" theories it can be assumed, that the two mechanisms are acting simultaneously. Therefore papillectomy seems to be an incompetent experimental model to draw conclusions as to an "isolated" regulatory function of the macula densa.
Literature DAUDA, G., M. SZOKOL and P. ENDES, Correlation between renal renin content and number of juxtaglomerular granular cells. Acta Physiol. Acad. Sci. Hung. 33, 27~30 (1968). DAVIES, D. J., Changes in the renal cortex following experimental medullary necrosis. Arch. Path. 86,377-394 (1968). DEVENYI, I., G. DAUDA and J. SZABO, Juxtaglomerular index and activity of the renin-angiotensin system. Path. Europ. 6, 19-33 (1971). .. ENDES, P., I. DEVENYI, G. KRAUSZ und V. SZOKOLY, Uber die Rolle der juxtaglomerularen granulierten Zellen in der Autoregulation des Nierenkreislaufes. Zschr. Ges. Exp. Med. 138, 271-276 (1964). - Sz. GOMBA and 1. DEVENYI, Specific staining and exact quantitative evaluation of the granulation in the juxtaglomerular cells. Acta Morph. Acad. Sci. Hung. 11, 189-193 (1969). FLAMENBAUM, W., R. J. HAMBURGER, M. HUDDLESTON and L. TEMPLEMAN, Superficial and deep juxtaglomerular apparatus renin activity of the rat kidney. Effect of surgical preparation and NaCl intake. J. Clin. Invest. 54, 1373-1381 (1974). GROSS, F., H. BRUNNER and M. ZIEGEL, Renin-angiotensin system, aldosterone and sodium balance. Recent Progr. in Hormone Res. 21, 119-177 (1965). HARTROFT, P. M., and W. S. HARTROFT, Studies on renal juxtaglomerular cells. 1. Variations produced by sodium chloride and desoxycorticosterone acetate. J. Exp. Med. 97, 415-427 (1953). KROON, D. B., J. F. JENKING and J. H. WISSE, Reaction of the renal papilla in rats. Experientia 18,581-583 (1962). MARSCHALL, S., T. B. MILLER and A. E. FARAH, Effect of renal papillectomy on ability of the hamster to concentrate urine. Amer. J. PhysioI. 204, 363-368 (1963). MUNKACSI, I., and M. PALKOVITS, Study on the renal pyramid, loops of Henle and percentage distribution of their thin segment in mammals living in desert, semidesert and waterrich environment. Acta BioI. Hung. 17, 89-104 (1966). REEVES, G., and S. C. SOMMERS, Sensitivity of the renal macula densa to urinary sodium. Proc. Soc. Exp. BioI. Med. 120, 324-332 (1965). ROJO-ORTEGA, J. M., and J. GENEST, Index de l'activite histochimique de la glucose-6-phosphate dehydrogenase dans la «macula densa» (IMD) et sa distribution dans Ie cortex renal chez Ie rat. Path. BioI. 18, 595-599 (1970). STEMEY, T. A., Some observations on the filtration fraction, on the transport of the sodium and water in the ischemic kidney and on prognostic importance of RPF to the contralateral kidney in renovascular hypertension. In: Antihypertensive Therapy, Ed. F. GROSS, pp.632. Springer Verlag, Berlin-Heidelberg-New York 1966. THURAU, K., und J. SCHNERMANN, Die Natriumkonzentration an den macula-densa-Zellen als regulierender Factor fiir das Glomerulusfiltrat. (Mikropunktionsversuche.) Klin. Wschr. 43, 410-413 (1965).
74
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Influence of sodium concentration at macula densa cells on tubular sodium load. Ann. N. Y. Acad. Sci. 139, 388-399 (1966). - J. SCHNERMANN, W. NAGEL, M. HORSTER and M. WAHL, Composition of tubular fluid in the macula densa segment as a factor regulating the function of the juxtaglomerular apparatus. Circ. Res. 20-21, Suppl. 2., 69-75 (1967). TOBIAN L. A. TOMBULIAN and J. JANECEK, The effect of high perfusion pressures on the granulation of juxtaglomerular cells in an isolated kidney. J. CHn. Invest. 38, 605-610 (1959). TRIBE, C. R., and R. H. HEPTINSTALL, The juxtaglomerular apparatus in scarred kidney. Brit. J. Exp. Path. 46, 339-347 (1965). VANDER, A. J., Control of renin release. Physiol. Rev. 47, 359-382 (1967). Author's address: Dr. M. SZOKOL, Department of Pathology, Uniyersity Medical School, POB 22. H - 4012 Debrecen, Hungary.
75
The effect of unilateral papillectomy on the juxtaglomerular granulated cells By M. SZOKOL, E. BARANYAI1 ), 1. MIK( 2) and Sz. GOMBA With 2 figures (Received February 27, 1977) Key words: papillectomy; juxtaglomerular granulated cells; glomeruli; renin-angiotensin system macula densa; sodium excretion; glomerular perfusion; kidney; macular cells; glomerular filtration rate; juxtaglomerular index; nephron; tubular sodium load; rat Abbreviations: JCG = juxtaglomerular granulated cells JGI = juxtaglomerular index GFR = glomerular filtration rate
Summary The changes of the juxtaglomerular index values in the superficial, deep and whole cortical areas of rat kidneys after unilateral papillectomy were analyzed. On the papillectomized side the JGI values showed an increase in the deep, and a decrease in the superficial cortical zone. The changes proved to be significant during the whole experimental period in the juxtamedullary index and between the 4~14 postoperative days in the superficial index values. The tendency of the changes of JGI in the contralateral kidneys was similar to those of the papillectomized kidneys, but significant differences were registered less constantly. These changes are probably the consequences of haemodynamic factors. Papillectomy is considered an incompetent model for studying the regulatory function of macula densa in the synthesis of renin.
The macula densa plays an important role in the fine regulation of the glomerular perfusion and sodium excretion (THURAU 1965, 1967, GROSS 1965, STElIlEY 1966, VANDER 1967). The macular cells seem to transmit humoral information to the juxtaglomerular granulated cells (JGC) about the sodium content of the distal tubular fluid (REEVES 1965). These modified smooth muscle cells of the arteriolar wall synthetise renin and are indirectly responsible for the production of angiotensin II. Two different theories explain how the GFR and the sodium excretion are regulated by the renin-angiotensin system. According to THURAU'S conception (1965, 1966, 1967) the high tubular sodium content (concentration) induces renin production and secretion. The secreted renin forms angiotensin "in loco", which gives rise to a contraction of the afferent arterioles lowering the GFR and the rate of filtrated sodium. On the contrary, VANDER et al. (1967) regard the low tubular sodium load as a specific stimulatory effect on the synthesis and secretion of renin. The effect of locally produced angiotensin II may be a contraction in the efferent arterioles followed by a rise in the GFR and an increase of the filtrated sodium. 1) Present address: Pediatric Clinic, University Medical School, Debrecen, Hungary. 2) Present address: Department of Experimental Surgery, University Medical School, Debrecen, Hungary.
69
In order to confirm one of these conceptions and to study the interactions between the macula densa and the juxtaglomerular granulated cells, unilateral papillectomy was performed in the right kidney of rats. Breaking the continuity of some nephrons, first of all the juxtamedullary ones by papillectomy, the "feed-back" mechanism between the macula densa and the glomerular hilus are blocked in the same nephrons, too. The purpose of our investigations was to find out changes in the juxtaglomerular index rates (JGI) after the operation. Within certain limits, the JGI properly represents the functional state of these cells (DEVENYI et aI. 1971, HARTROFT and HARTROFT 1963, DAuDA et aI. 1968).
Material and methods Male Wistar rats of our own breeding weighing about 160-180 g were used for the experiment. Papillectomy was carried out on the right kidneys of 15 animals according to the method of KROON et al. (1962). The parenchyma was incised and the capsule sutured of the right kidneys of 5 sham-operated control rats. A standard normal diet and tap water were offered ad lib. Water intake of all rats was registered on the 3rd, 7th, 13th and 162nd postoperative days. Urine samples were collected in special cages for 24 hours at the same time. Urine volume and specific weight were measured. The specific weight was determined by means of a pycnometer comparing the weight of equal volumes of urine and distilled water at 4°C. On the 4th, 8th, 14th and 163rd days after the operation 4-4 papillectomized rats and 1 control were killed in ether anesthesia by bleeding. Kidneys were fixed in 10% neutralized formol. Blocks were cut out omitting the linear scar of the 6peration and its immediate surroundings and were embedded in paraffin. 5 micron thick sections were stained by hemalum-eosin and by the combined trichrome method (ENDES 1969) in order to visualize the JGC. The JGI was estimated after the method of HARTROFT and HARTROFT (1953) modified by ENDES et al. (1969) counting at lease 400 glomeruli in each kidney. The JGI rates of the whole area of the cortex and the inner (juxeamedullary) corticll zone were determined separately. From these data we calculated the JG I values belonging to the outer cortical zone. In order to count the JGI of the juxtamedullary cortical area, the outer cortical zone was shaded by painting the cover glass with Indian ink under microscopic control. The significance of differences between mean values of JG I, water intake, urinary output and specific weight was estimated by STUDENT'S t-test.
Results The effectiveness of the papillectomy was pointed out by the increase in the daily water intake and urinary output during the postoperative period (table 1). The urinary specific weight was diminished to 1036.7 in comparison with the 1042 control value. All these changes proved to be significant and are similar to the data of the literature referring to bilateral papillectomy (KROON et aI. 1962). The values, measured at unilateral papillectomy are somewhat lower than after bilateral operation. The general histological picture of the papillectomized kidneys was similar to that formed by LUCKE et al. (1968) and DAVIES (1968) except that both tubular atrophy and chronic interstitial inflammation was less pronounced (fig. 1, 2). The JGI rates of the superficial, juxtamedullary, and whole cortical areas in both kidneys of the control rats were identical with the data of the literature (ROJO-ORTEGA and GENEST 1970). Table 1. Some physiological parameters of unilaterally papillectomized and sham-operated control rats (mean values ± SEM) Papillectomized rats n = 60 Water intake
(mlf24 hours)
Urinary volume (mlj24 hours) Urinary specific weight (mg/ml)
36.75 ± 1.28*
25.78
± 1.46
± 0.36*
5.64
± 0.53
± 1.83*
1042.05
8.24 1036.7
*) p < 0.001 as compared with controls.
70
Controls
n = 15
± 2.6
Fig. U',Cut surface of the papillectomy covered by cuboidcylindrical epithelium. 14th day after the operation. HE. x 63.
Fig. 2. Well preserved cortical area in the papillectomized kidney. 7th day after the operation. HE x50.
71
-::J ~
Table 2. Juxtaglomerular index values (JGI) of the superficial, deep and whole cortical areas in the papillectomized and untouched kidneys between the 4-163 postoperative days (mean values ± SEM) Days after the unilateral papillectomy 4 8 14 24 163 Controls
JGI . Papillectomized kidneys cortical area deep super~icial
whole
JGI Untouched kidneys cortical area superficial
± 1.96** 10.00 ± 1.88*** 11.24 ± 1.87*** 19.94 ± 5.18 26.00 ± 2.09 27.62 ± 2.2
± 0.84** 19.41 ± 1.8 18.39 ± 1.93 21.78 ± 1.4 24.5 ± 1.63 22.9 ± 1.79
± 3.09* 21.05 ± 2.53 26.2 ± 3.34 15.08 ± 1.95** 21.9 ± 2.93 27.62 ± 2.2
12.45
± 3.9* 33.21 ± 6.12*** 38.94 ± 3.58*** 30.1 ± 4.37** 22.2 ± 3.11* 13.61 ± 2.94 24.31
* p < 0.05 as compared with controls. ** p < 0.01 as compared with controls. *** p < 0.001 as compared with controls.
16.83
15.93
deep
± 4.02 24.98 ± 3.83* 26.84 ± 2.49** 18.88 ± 2.18 23.0 ± 3.12* ·13.61 ± 2.94 15.82
whole
± 1.72* 23.52 ± 3.26 27.66 ± 1.9 17.21 ± 2.22 20.9 ± 2.35 22.9 ± 1.79 15.65
The most prevalent changes were observed in the juxtamedullary cortical area of the papillectomized kidneys. The JGI values of this area proved to be significantly higher during the whole experimental period as compared to the controls. The peak of the elevation was found on the 8th postoperative day. Thereafter the JGI rates decreased gradually till the 163rd day, but did not sink to the control level. In the superficial cortical area of the papillectomized kidneys the JGI values were·found to be below the control rates. The initial decrease was followed by a gradual elevation till the 163rd day. The differences to the controls are significant on the 4th, 8th, and 14th postoperative days. The changes of the JGI rates in the contralateral kidneys were similar to the papillectomized ones, first of all in the juxtamedullary area, where also an elevation could be registered during the whole experimental period, but values proved to be significantly higher than the controls only on the 8th, 14th, and 163rd days. A significant increase was registered in the superficial index rates on the 4th and 24th days. None of the changes were expressed in the JGI of the whole cortical area except the rates on the 4th postoperative day, when they were decreased significantly both in the right and left kidneys. The mean values and standard errors of the JGI belonging to different cortical zones are summarized in table 2.
Discussion There are no data in the literature about the changes of the JGI after papillectomy. TRIBE and HEPTINSTALL (1965) described hyperplasia and hypergranulation of the JG cells after a simple incision of the cortical and medullary zone of the kidney. The alterations were observed in an irregular distribution in the neighbourhood of the scars, therefore JGI values could not be estimated. Hyperplasia of the JG cells was explained with the scarring. In our material fibrosis or scarring did not occur in the sections used for the estimation of the JGI. We made a distinction between the superficial and deep glomeruli, because the interrupted nephrons were probably situated in the deep cortical area. Only the Henle's loops belonging to the deep nephrons reach the tip of the papilla. The loops of superficial nephrons end at the borderline of the outer and inner medulla (MUNKACSI and PALKOVITS 1966). Among the observed changes of the JGI the increase in the juxtamedullary area seems to be the most distinct one, first of all on the papillectomized side, but this tendency is manifested in the contralateral kidney, too. The elevation on the papillectomized side can be explained by VANDER'S theory (1967): Interrupting the deep nephrons the sodium concentration falls to 0 in the tubular lumen at the level of the macula densa. The increase in the granularity of the JG cell - representing most probably an elevated renin production (DAUDA et al. 1968, DEVENYI et al. 1971) - is elicited by the decreased tubular sodium load. But the subsequent results of our experiment put to issue the validity of the above mentioned conclusion: In the contralateral kidney containing intact nephrons, significantly elevated JGI values were also registered in the deep cortical zone. The observed decrease of the JGI in the bilateral superficial cortical areas cannot be explained by primary changes occuring in the tubular sodium load at the macula densa. It is much more probable that the changes of the JGI in both kidneys are produced by haemodynamic alterations. TOBIAN et al. (1959) and ENDES et al. (1964) traced the hypergranularity of the JG cells back to the decreased stretching of the afferent arteriolar wall and inversely, the hypogranulation back to the increased arteriolar stretching in accordance with the assumed baroreceptor function of these cells. The interruption of the efferent arterioles originating from the juxtamedullary glomeruli (arteriolae rectae spuriae) obviously leads to haemodynamic consequences in the deep cortical area. Further reflectoric changes can be assumed in the circulation of the superficial cortical area of the papillectomized kidney and of both cortical areas of the contralateral kidney.
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According to the microdissection studies of FLAMENBAUM et al. (1974) decreased blood flow to superficial cortex promotes renin release and results in decreased superficial JGA renin content, while increased deeper cortical flow may inhibit renin release resulting in increased deep JGA renin content. If we consider our superficial and deep JGI values, changes of an opposed sign are to be induced in the superficial and deep cortical circulation, i. e. the blood flow of the deeper cortex probably increased. On the other hand it must be taken into consideration that the granularity of the JG cells is influenced by the synthesis, secretion and storage of renin. That means, the synthetic activity is not characterised by the JGI values alone, but together with the renin concentration in the blood serum and in the renal tissue (DEVENYI et al. 1971). The most reliable parameter of renal renin release is the renin concentration in the blood of renal vein, but this value does not reflect separated superficial and deep cortical renin release. Another factor, which might influence the renin production in papillectomized rats is that these animals are polyuric (KROON et al. 1962, MARSCHALL et al. 1963) and probably mildly sodium losing, although we have not found data in the literature about their sodium metabolism. Considering the "baroreceptor" and "macula densa" theories it can be assumed, that the two mechanisms are acting simultaneously. Therefore papillectomy seems to be an incompetent experimental model to draw conclusions as to an "isolated" regulatory function of the macula densa.
Literature DAUDA, G., M. SZOKOL and P. ENDES, Correlation between renal renin content and number of juxtaglomerular granular cells. Acta Physiol. Acad. Sci. Hung. 33, 27~30 (1968). DAVIES, D. J., Changes in the renal cortex following experimental medullary necrosis. Arch. Path. 86,377-394 (1968). DEVENYI, I., G. DAUDA and J. SZABO, Juxtaglomerular index and activity of the renin-angiotensin system. Path. Europ. 6, 19-33 (1971). .. ENDES, P., I. DEVENYI, G. KRAUSZ und V. SZOKOLY, Uber die Rolle der juxtaglomerularen granulierten Zellen in der Autoregulation des Nierenkreislaufes. Zschr. Ges. Exp. Med. 138, 271-276 (1964). - Sz. GOMBA and 1. DEVENYI, Specific staining and exact quantitative evaluation of the granulation in the juxtaglomerular cells. Acta Morph. Acad. Sci. Hung. 11, 189-193 (1969). FLAMENBAUM, W., R. J. HAMBURGER, M. HUDDLESTON and L. TEMPLEMAN, Superficial and deep juxtaglomerular apparatus renin activity of the rat kidney. Effect of surgical preparation and NaCl intake. J. Clin. Invest. 54, 1373-1381 (1974). GROSS, F., H. BRUNNER and M. ZIEGEL, Renin-angiotensin system, aldosterone and sodium balance. Recent Progr. in Hormone Res. 21, 119-177 (1965). HARTROFT, P. M., and W. S. HARTROFT, Studies on renal juxtaglomerular cells. 1. Variations produced by sodium chloride and desoxycorticosterone acetate. J. Exp. Med. 97, 415-427 (1953). KROON, D. B., J. F. JENKING and J. H. WISSE, Reaction of the renal papilla in rats. Experientia 18,581-583 (1962). MARSCHALL, S., T. B. MILLER and A. E. FARAH, Effect of renal papillectomy on ability of the hamster to concentrate urine. Amer. J. PhysioI. 204, 363-368 (1963). MUNKACSI, I., and M. PALKOVITS, Study on the renal pyramid, loops of Henle and percentage distribution of their thin segment in mammals living in desert, semidesert and waterrich environment. Acta BioI. Hung. 17, 89-104 (1966). REEVES, G., and S. C. SOMMERS, Sensitivity of the renal macula densa to urinary sodium. Proc. Soc. Exp. BioI. Med. 120, 324-332 (1965). ROJO-ORTEGA, J. M., and J. GENEST, Index de l'activite histochimique de la glucose-6-phosphate dehydrogenase dans la «macula densa» (IMD) et sa distribution dans Ie cortex renal chez Ie rat. Path. BioI. 18, 595-599 (1970). STEMEY, T. A., Some observations on the filtration fraction, on the transport of the sodium and water in the ischemic kidney and on prognostic importance of RPF to the contralateral kidney in renovascular hypertension. In: Antihypertensive Therapy, Ed. F. GROSS, pp.632. Springer Verlag, Berlin-Heidelberg-New York 1966. THURAU, K., und J. SCHNERMANN, Die Natriumkonzentration an den macula-densa-Zellen als regulierender Factor fiir das Glomerulusfiltrat. (Mikropunktionsversuche.) Klin. Wschr. 43, 410-413 (1965).
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Influence of sodium concentration at macula densa cells on tubular sodium load. Ann. N. Y. Acad. Sci. 139, 388-399 (1966). - J. SCHNERMANN, W. NAGEL, M. HORSTER and M. WAHL, Composition of tubular fluid in the macula densa segment as a factor regulating the function of the juxtaglomerular apparatus. Circ. Res. 20-21, Suppl. 2., 69-75 (1967). TOBIAN L. A. TOMBULIAN and J. JANECEK, The effect of high perfusion pressures on the granulation of juxtaglomerular cells in an isolated kidney. J. CHn. Invest. 38, 605-610 (1959). TRIBE, C. R., and R. H. HEPTINSTALL, The juxtaglomerular apparatus in scarred kidney. Brit. J. Exp. Path. 46, 339-347 (1965). VANDER, A. J., Control of renin release. Physiol. Rev. 47, 359-382 (1967). Author's address: Dr. M. SZOKOL, Department of Pathology, Uniyersity Medical School, POB 22. H - 4012 Debrecen, Hungary.
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